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6253 (T > C)

General info

Mitimpact ID
MI.2629
Chr
chrM
Start
6253
Ref
T
Alt
C
Gene symbol
MT-CO1 Extended gene annotation
Gene position
350
Gene start
5904
Gene end
7445
Gene strand
+
Codon substitution
ATA/ACA
AA pos
117
AA ref
M
AA alt
T
Functional effect
missense
OMIM ID
516030
HGVS
NC_012920.1:g.6253T>C
HGNC ID
7419
RC complex
IV
Ensembl gene ID
ENSG00000198804
Ensembl protein ID
ENSP00000354499
Ensembl transcript ID
ENST00000361624
Uniprot ID
P00395
Uniprot name
COX1_HUMAN
Ncbi gene ID
4512
Ncbi protein ID
YP_003024028.1
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Conservation

PhyloP 100v
1.968 Conservation Score
PhyloP 470way
0.361 Conservation Score
PhastCons 100v
0.973 Conservation Score
PhastCons 470way
0.479 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Tolerated Score and details of the predictor
Mutation Assessor
Medium Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
High impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
692631
Clinvar ALLELEID
681167
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Leigh syndrome
Clinvar CLNSIG
Benign
MITOMAP Allele
6253T>C
MITOMAP Disease Clinical info
Prostate cancer / enriched in poag cohort
MITOMAP Disease Status
Reported
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.9684%
MITOMAP General GenBank Seqs
592
MITOMAP General GenBank Curated refs
10720328 19267350 24467713 11938495 27217714 16721903 15647368 18545700 29343773 19818876 20304802 16892079 16714301
MITOMAP Variant Class
polymorphism;disease
Gnomad AN
56427
Gnomad AC hom
656
Gnomad AF hom
0.0116256
Gnomad AC het
1
Gnomad AF het
1.77e-05
Gnomad filter
Pass
HelixMTdb AC hom
997
HelixMTdb AF hom
0.0050871
HelixMTdb AC het
7
HelixMTdb AF het
3.57e-05
HelixMTdb mean ARF
0.28737
HelixMTdb max ARF
0.66426
ToMMo JPN54K AC
555
ToMMo JPN54K AF
0.010221
ToMMo JPN54K AN
54302
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
14.09 CPD variant frequency
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

6253 (T > A)

General info

Mitimpact ID
MI.2630
Chr
chrM
Start
6253
Ref
T
Alt
A
Gene symbol
MT-CO1 Extended gene annotation
Gene position
350
Gene start
5904
Gene end
7445
Gene strand
+
Codon substitution
ATA/AAA
AA pos
117
AA ref
M
AA alt
K
Functional effect
missense
OMIM ID
516030
HGVS
NC_012920.1:g.6253T>A
HGNC ID
7419
RC complex
IV
Ensembl gene ID
ENSG00000198804
Ensembl protein ID
ENSP00000354499
Ensembl transcript ID
ENST00000361624
Uniprot ID
P00395
Uniprot name
COX1_HUMAN
Ncbi gene ID
4512
Ncbi protein ID
YP_003024028.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
1.968 Conservation Score
PhyloP 470way
0.361 Conservation Score
PhastCons 100v
0.973 Conservation Score
PhastCons 470way
0.479 Conservation Score

Pathogenicity predictors

PolyPhen2
Benign Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Tolerated Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely pathogenic Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
Medium Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Pathogenic Score and details of the meta-predictor
APOGEE2
Vus- Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
Neutral Score and details of the meta-predictor
MtoolBox
Neutral Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Medium impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
6253T>A
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 6253 (T/C) 6253 (T/A)
~ 6253 (ATA/ACA) 6253 (ATA/AAA)
MitImpact id MI.2629 MI.2630
Chr chrM chrM
Start 6253 6253
Ref T T
Alt C A
Gene symbol MT-CO1 MT-CO1
Extended annotation mitochondrially encoded cytochrome c oxidase I mitochondrially encoded cytochrome c oxidase I
Gene position 350 350
Gene start 5904 5904
Gene end 7445 7445
Gene strand + +
Codon substitution ATA/ACA ATA/AAA
AA position 117 117
AA ref M M
AA alt T K
Functional effect general missense missense
Functional effect detailed missense missense
OMIM id 516030 516030
HGVS NC_012920.1:g.6253T>C NC_012920.1:g.6253T>A
HGNC id 7419 7419
Respiratory Chain complex IV IV
Ensembl gene id ENSG00000198804 ENSG00000198804
Ensembl transcript id ENST00000361624 ENST00000361624
Ensembl protein id ENSP00000354499 ENSP00000354499
Uniprot id P00395 P00395
Uniprot name COX1_HUMAN COX1_HUMAN
Ncbi gene id 4512 4512
Ncbi protein id YP_003024028.1 YP_003024028.1
PhyloP 100V 1.968 1.968
PhyloP 470Way 0.361 0.361
PhastCons 100V 0.973 0.973
PhastCons 470Way 0.479 0.479
PolyPhen2 benign benign
PolyPhen2 score 0.0 0.01
SIFT neutral neutral
SIFT score 0.37 0.16
SIFT4G Tolerated Tolerated
SIFT4G score 0.321 0.063
VEST Neutral Neutral
VEST pvalue 0.5 0.28
VEST FDR 0.55 0.55
Mitoclass.1 neutral damaging
SNPDryad Neutral Neutral
SNPDryad score 0.01 0.69
MutationTaster . .
MutationTaster score . .
MutationTaster converted rankscore . .
MutationTaster model . .
MutationTaster AAE . .
fathmm . .
fathmm score . .
fathmm converted rankscore . .
AlphaMissense likely_benign likely_pathogenic
AlphaMissense score 0.1414 0.7365
CADD Neutral Neutral
CADD score -0.640752 0.688621
CADD phred 0.099 8.752
PROVEAN Tolerated Damaging
PROVEAN score -2.08 -2.75
MutationAssessor medium medium
MutationAssessor score 2.62 3.17
EFIN SP Neutral Neutral
EFIN SP score 0.794 0.664
EFIN HD Neutral Neutral
EFIN HD score 0.984 0.408
MLC Neutral Neutral
MLC score 0.32337498 0.32337498
PANTHER score . .
PhD-SNP score . .
APOGEE1 Pathogenic Pathogenic
APOGEE1 score 0.67 0.53
APOGEE2 Benign VUS-
APOGEE2 score 0.0529658508394979 0.302163785176961
CAROL neutral neutral
CAROL score 0.63 0.84
Condel deleterious deleterious
Condel score 0.69 0.58
COVEC WMV neutral neutral
COVEC WMV score -3 -3
MtoolBox neutral neutral
MtoolBox DS 0.13 0.23
DEOGEN2 . .
DEOGEN2 score . .
DEOGEN2 converted rankscore . .
Meta-SNP . .
Meta-SNP score . .
PolyPhen2 transf high impact medium impact
PolyPhen2 transf score 2.07 1.12
SIFT_transf medium impact medium impact
SIFT transf score 0.06 -0.21
MutationAssessor transf medium impact medium impact
MutationAssessor transf score 0.86 1.89
CHASM Neutral Neutral
CHASM pvalue 0.34 0.64
CHASM FDR 0.9 0.9
ClinVar id 692631.0 .
ClinVar Allele id 681167.0 .
ClinVar CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 .
ClinVar CLNDN Leigh_syndrome .
ClinVar CLNSIG Benign .
MITOMAP Disease Clinical info Prostate Cancer / enriched in POAG cohort .
MITOMAP Disease Status Reported .
MITOMAP Disease Hom/Het +/- ./.
MITOMAP General GenBank Freq 0.9684% .
MITOMAP General GenBank Seqs 592 .
MITOMAP General Curated refs 10720328;19267350;24467713;11938495;27217714;16721903;15647368;18545700;29343773;19818876;20304802;16892079;16714301 .
MITOMAP Variant Class polymorphism;disease .
gnomAD 3.1 AN 56427.0 .
gnomAD 3.1 AC Homo 656.0 .
gnomAD 3.1 AF Hom 0.0116256 .
gnomAD 3.1 AC Het 1.0 .
gnomAD 3.1 AF Het 1.7722e-05 .
gnomAD 3.1 filter PASS .
HelixMTdb AC Hom 997.0 .
HelixMTdb AF Hom 0.005087176 .
HelixMTdb AC Het 7.0 .
HelixMTdb AF Het 3.5717385e-05 .
HelixMTdb mean ARF 0.28737 .
HelixMTdb max ARF 0.66426 .
ToMMo 54KJPN AC 555 .
ToMMo 54KJPN AF 0.010221 .
ToMMo 54KJPN AN 54302 .
COSMIC 90 . .
dbSNP 156 id . .
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend